Fred Hutch clinical researchers win Consortium grants

Four research teams from the Hutchinson Center and University of Washington have won awards to support early phase clinical trials from the Fred Hutchinson/University of Washington Cancer Consortium Cancer Center Support Grant.

These awards are given to innovative, proof-of-principle early clinical studies that have the potential to lead to larger clinical trials in the future. The awards, totaling nearly $120,000, support research nurses or data managers on the studies for one year.

This year’s funded studies include tests of:

• A drug to lower treatment-related mortality in elderly patients with acute myeloid leukemia (AML)
• New treatment for AML relapse
• Novel immunotherapy for Merkel cell carcinoma
• New treatment for head and neck cancer

The 2012-2013 projects are:

Drs. Roland Walter and Eli Estey, Clinical Research Division
A gentler treatment for AML

Chemotherapy can be especially toxic for elderly AML patients or those with additional health problems; these patients need alternative treatments to fight their cancer. The drug CPX-351, which combines two chemotherapy drugs, shows promise as a gentler treatment for AML, and has already been shown to yield good remission rates in early clinical trials. Walter and Estey will test two doses of CPX-351 in AML patients to determine the best dose to use in a larger, phase 2 trial to be conducted through SWOG.

Drs. Rajeev Rajendra, Derek Stirewalt and Roland Walter, Clinical Research Division
Reversing epigenetic silencing in patients with AML relapse

Relapse is common in AML patients, and unfortunately those who relapse often fare poorly, with remission rates of only 15 percent for those who have relapsed within a year of their initial treatment. Epigenetics, heritable modifications to DNA that don’t change the actual genetic code, are known to play a role in AML. Important genes are aberrantly silenced by rogue DNA methylation in leukemic cells. The researchers will test decitabine, a drug that reverses DNA methylation, in combination with standard chemotherapy for patients with AML relapse in the hope that reactivating these silenced genes helps lead to remission. The study will test different durations decitabine to determine the best dose for a larger clinical trial.

Dr. Shailender Bhatia, University of Washington, Medical Oncology
Boosting T-cells to battle Merkel cell carcinoma

Merkel cell carcinoma (MCC), an aggressive skin cancer, is caused by infection with Merkel cell polyomavirus. Bhatia’s group has found that microenvironments surrounding these tumors, immune cells, specifically T-cells, are surprisingly lacking despite the presence of foreign protein pieces from the virus. They have also found that those patients who have more T-cells in and around the tumor have a higher chance of survival. Bhatia’s group will test whether a drug to boost T-cell trafficking to the tumor will improve outcomes for patients with this carcinoma. The researchers will test the drug Glucopyranosyl Lipid A, made by Seattle’s Immune Design Corp., in seven MCC patients and will ask whether the drug increases T-cell numbers in the tumor and slows the cancer’s progression.

Dr. Eduardo Méndez, University of Washington, Otolaryngology: Head and Neck Surgery
Blocking Wee1 may improve survival for head and neck cancer patients

Squamous cell carcinoma of the head and neck (SCCHN) is the sixth most common cancer worldwide and has generally poor outcomes, with an overall five-year survival rate of less than 30 percent. SCCHN patients with mutations in the gene coding for the tumor protein p53 have especially poor outcomes. Mendez’ group found that the enzyme Wee1 plays a role in SCCHN tumor growth; disruption of this enzyme selectively stems the growth of tumor cells with mutated p53. The researchers will test the drug MK-1775, which blocks Wee1’s activity, in 12-15 head and neck cancer patients with mutated p53, to test the drug’s safety and effects on survival.